In the process of seeking better methods of protecting myocardial function during open heart operations, we are attempting to define the pathophysiology of myocardial deterioation during cardiopulmonary bypass and particularly during ischemia. Employing the isolated cross-perfused dog heart as an experimental model, we have correlated physiologic and biochemical data obtained during graded ischemia injuries under various conditions. We have recorded parameters of systolic function, diastolic compliance, and wall thickness. Biochemical parameters measured have included tissue glycogen, CPK, water content, and electrolytes. In the contracting heart and during plasma perfusion studies, we have measured transmyocardial pH, blood gases, and lactate. We have recently begun to measure tissue ATP levels, metabolites of ATP, creatine phosphate, calcium and magnesium tissue concentrations. We have produced myocardial contracture during reprefusion following prolonged ischemic arrest. We have characterized the gradations of ischemic injury and their relation to mechanical and biochemical failure. We are currently extending these observations to the isolated blood perfused heart rendered ischemic but protected by various interventions including potassium arrest, asanguinous (plasma) coronary washout, and hypothermia.